Drug-induced cardiotoxicity represents one of the most serious side-effects associated with drug development and is a common cause of attrition in preclinical and clinical development. It is also responsible for the post-market withdrawal of a number of clinically important drugs. Assessing the potential for cardiotoxicity is therefore a crucial step in the drug discovery and development process and several cardiac safety liability models have been established to enable the prediction of cardiotoxicity.
We recently presented our latest work in the field of cardiotoxicity at SOT 2021 entitled: A Combined In Vitro Approach for the Dual Detection of Functional and Structural Cardiotoxicity.
The poster describes the work conducted to demonstrate the dynamic relationship between structural and functional cardiotoxicity within a single cell population of human induced pluripotent cardiomyocytes (iPSC-CM’s) using a combination of cellular assays, potentially linking morphological changes with alterations in electrophysiological signatures. This combined profiling technique demonstrates a 100% sensitivity for both functional and structural cardiotoxicity liability, a 100% specificity for functional cardiotoxicity liability, and a 90% specificity for structural cardiotoxicity liability.
This approach shows it is possible to detect early cellular morphology changes and cytotoxicity alongside functional profiling thus improving the in vitro to in vivo translation of cardiotoxicity risk assessment for new chemical entities early in preclinical screening studies.
To find out more about this work, or to discuss a toxicology project with us, contact us.cardiomyocytes, cardiotoxicity, iPSC, safety, toxicology